Conditioned Pain Modulation

Conditioned Pain Modulation (CPM): A Conversation with Prof. David Yarnitsky, Head of the Neurology department, Rambam Medical Center, Haifa, Israel

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Professor Yarnitsky is a director at the neurology department, Rambam Health Care Campus. He is also the head of the clinical neurophysiology laboratory at the Technion (Haifa, Israel). His research focuses on pain, in the aspects of measurement, mechanism and therapy, migraine, autonomic disorders, and cerebrovascular disorders]

Q: What is Conditioned Pain Modulation / CPM?

A:CPM is a paradigm used in the lab where we use a conditioning stimulus to influence a test stimulus. The context is “pain inhibits pain”. CPM is a way to study the endogenous pain inhibition ability of the subject. The purpose is not to inhibit pain per se by applying another pain, but to learn about the inhibition ability.

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Q: What is CPM used for?

A:The first question that leads all pain researchers is why does the same disease or injury causes different pain levels in different people. One way to explain this is pain modulation: how does the nervous system of different individuals handle painful stimuli? The process of pain-inhibits-pain is a way to reflect an important mechanism of pain processing – the inhibitory mechanism. All people have a pain inhibition mechanism. The question is how well does this mechanism work. We know that the ability to inhibit pain in the lab reflects different clinical aspects of pain. For example, the tendency to develop post-operative chronic pain, responsiveness to a certain drug, etc”.

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Q: What are the major applications for CPM?

A:The most significant area is pain treatment – deciding on the most suitable drug according to the defective pain inhibition mechanism as tested with CPM. Until now, treating neuropathic pain is through trial and error. The physician would recommend one type of drug and it would take weeks or even months until one could decide whether the drug is efficient or not. Meanwhile, the patient continues to suffer…

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The second possible application is predicting future pain; for instance, post-operative pain, pain following an accident or trauma, etc.

The third possible application is prophylaxis. For example, in migraines, there is no way of knowing which drug would prevent migraines. If you can test the patient’s pain modulation, you can identify the defective mechanism and therefore prescribe a drug that would treat this specific mechanism. This way the patient would benefit from individualized tailored treatment. Another example would be proper preparation for an operation. If we know a specific operation is considered of high pain level, and we know the pain modulation profile of the patient, we can treat him with a suitable drug and provide maximum defense against the post-surgical pain syndrome.

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Q: What is the potential role of CPM in pharmaceutical / clinical trials?

A:A major problem of pharmacologic clinical trials is that often, very few people respond to the tested drug and when the results are analyzed, the conclusion is that the drug is not effective. The potential role of CPM here is in “enriched enrolment”. If we know the mechanism of action of a new potential drug, we can hypothesize which pain modulation mechanism would be affected by it. Potential enrolled subjects can be tested, looking for those individuals in which this specific mechanism is defected. If the pharmaceutical company would enroll only this population in their trial, they are bound to have better results. This area is still very new and additional research is still required.

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Q: Could you share your clinical research plans with CPM?

A: We are planning a study on post-surgical pain after bypass surgery, using two drugs that affect different mechanisms of pain modulation. We would try and see if giving the drug in advance would alter the nocicpeptive state of the patients and bring them closer to the anti-nociceptive part of the pain scale, thus reduce the occurrence of post-operative pain.